Marine Drugs

15 pages, 2004 KiB

Open AccessArticle

Metabolic Blockade-Based Genome Mining of Malbranchea circinata SDU050: Discovery of Diverse Secondary Metabolites

by Hu Yang, Xiaowei Luo, Zhuo Shang, Kunlong Li, Jian Cai, Yingying Chen, Longchao Xin and Jianhua Ju

Mar. Drugs 2025, 23(1), 50; https://doi.org/10.3390/md23010050 - 20 Jan 2025

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Abstract

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation [...] Read more.

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type M. circinata SDU050, alongside five additional metabolite classes, including three novel cytochalasins (7–9), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (1) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (1) and (−)-mycousnine (10) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus subtilis. These findings underscore the chemical diversity and biosynthetic potential of M. circinata SDU050 and highlight an effective strategy for exploring marine fungal metabolites. Full article

(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)

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23 pages, 9793 KiB

Open AccessArticle

Deep-Sea-Derived Isobisvertinol Targets TLR4 to Exhibit Neuroprotective Activity via Anti-Inflammatory and Ferroptosis-Inhibitory Effects

by Zi-Han Xu, Ming-Min Xie, Chun-Lan Xie, Xian-Wen Yang and Jun-Song Wang

Mar. Drugs 2025, 23(1), 49; https://doi.org/10.3390/md23010049 - 20 Jan 2025

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Abstract

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, [...] Read more.

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development. In this study, we isolated 44 natural products from deep-sea-derived fungi and identified isobisvertinol (17) as a compound with anti-inflammatory and ferroptosis-inhibiting effects. Using LPS-induced microglial inflammation and RSL3-induced neuronal ferroptosis models, we found that 17 targets TLR4 to provide neuroprotection. Molecular docking studies revealed that 17 inhibits TLR4 activation by occupying the hydrophobic pocket at the TLR4-MD2 binding site. Additionally, 17 suppresses TLR4, reducing p38 MAPK phosphorylation, and inhibits ferroptosis by decreasing lipid peroxidation and modulating mitochondrial membrane potential. Metabolomic analysis showed that 17 rescues alterations in multiple metabolic pathways induced by RSL3 and increases levels of antioxidant metabolites, including glutamine, glutamate, and glutathione. In summary, our results indicate that isobisvertinol (17) targets TLR4 in neural cells to reduce inflammation and inhibit p38 MAPK phosphorylation, while regulating metabolic pathways, mainly GSH synthesis, to provide antioxidant effects and prevent ferroptosis in neurons. Full article

(This article belongs to the Section Marine Pharmacology)

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16 pages, 2179 KiB

Open AccessArticle

Ishophloroglucin A Isolated from Ishige okamurae Protects Glomerular Cells from Methylglyoxal-Induced Diacarbonyl Stress and Inhibits the Pathogenesis of Diabetic Nephropathy

by Chi-Heung Cho, Min-Gyeong Kim, Bomi Ryu and Sang-Hoon Lee

Mar. Drugs 2025, 23(1), 48; https://doi.org/10.3390/md23010048 - 20 Jan 2025

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Abstract

Ishige okamurae (I. okamuare), an edible brown alga, is rich in isophloroglucin A (IPA) phlorotannin compounds and is effective in preventing diseases, including diabetes. We evaluated its anti-glycation ability, intracellular reactive oxygen species scavenging activity, inhibitory effect on the accumulation of [...] Read more.

Ishige okamurae (I. okamuare), an edible brown alga, is rich in isophloroglucin A (IPA) phlorotannin compounds and is effective in preventing diseases, including diabetes. We evaluated its anti-glycation ability, intracellular reactive oxygen species scavenging activity, inhibitory effect on the accumulation of intracellular MGO/MGO-derived advanced glycation end products (AGE), and regulation of downstream signaling pathways related to the AGE–receptor for AGEs (RAGE) interaction. IPA (0.2, 1, and 5 μM) demonstrated anti-glycation ability by inhibiting the formation of glucose-fructose-BSA-derived AGEs by up to 54.63% compared to the untreated control, reducing the formation of irreversible cross-links between MGO-derived AGEs and collagen by 67.68% and the breaking down of existing cross-links by approximately 91% (p < 0.001). IPA protected cells from MGO-induced oxidative stress by inhibiting intracellular MGO accumulation (untreated cells: 1.62 μg/mL, MGO treated cells: 25.27 μg/mL, and IPA 5 μM: 11.23 μg/mL) (p < 0.001) and AGE generation and inhibited MGO-induced renal cell damage via the downregulation of MGO-induced RAGE protein expression (relative protein expression levels of MGO treated cells: 9.37 and IPA 5 μM:1.74) (p < 0.001). Overall, these results suggest that IPA has the potential to be utilized as a useful natural agent for the prevention and management of AGE-related diabetic nephropathy, owing to its strong anti-glycation activity. Full article

(This article belongs to the Special Issue Marine Natural Products in Anti-obesity and Metabolic Syndrome)

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14 pages, 5617 KiB

Open AccessArticle

Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways

by Jing Huang, Lei Li, Liyan Xu, Lixin Feng, Yuxin Wang, Attila Gabor SIK, Meng Jin, Rongchun Wang, Kechun Liu and Xiaobin Li

Mar. Drugs 2025, 23(1), 47; https://doi.org/10.3390/md23010047 - 19 Jan 2025

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Abstract

Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate (MBD), a compound derived from marine [...] Read more.

Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate (MBD), a compound derived from marine organisms, especially in IBD, using a zebrafish model. The results indicated that MBD could inhibit the inflammatory responses induced by CuSO₄, tail amputation and LPS in zebrafish. Furthermore, MBD notably inhibited the intestinal migration of immune cells, enhanced the integrity of the gut mucosal barrier and improved intestinal peristalsis function in a zebrafish IBD model induced by trinitro-benzene-sulfonic acid (TNBS). In addition, MBD could inhibit ROS elevation induced by TNBS. Network pharmacology analysis, molecular docking, transcriptomics sequencing and RT-PCR were conducted to investigate the potential mechanism. The results showed that MBD could regulate the TLR/NF-κB pathways by inhibiting the mRNA expression of TNF-α, NF-κB, IL-1, IL-1β, IL6, AP1, IFNγ, IKKβ, MyD88, STAT3, TRAF1, TRAF6, NLRP3, NOD2, TLR3 and TLR4, and promoting the mRNA expression of IL4, IκBα and Bcl-2. In conclusion, these findings indicate that MBD could be a potential candidate for the treatment of IBD. Full article

(This article belongs to the Special Issue Marine-Derived Ingredients for Functional Foods)

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20 pages, 3444 KiB

Open AccessArticle

Antimicrobial Activities of Polysaccharide-Rich Extracts from the Irish Seaweed Alaria esculenta, Generated Using Green and Conventional Extraction Technologies, Against Foodborne Pathogens

by Ailbhe McGurrin, Rahel Suchintita Das, Arturo B. Soro, Julie Maguire, Noelia Flórez Fernández, Herminia Dominguez, Maria Dolores Torres, Brijesh K. Tiwari and Marco Garcia-Vaquero

Mar. Drugs 2025, 23(1), 46; https://doi.org/10.3390/md23010046 - 18 Jan 2025

Viewed by 1121

Abstract

A rise in antimicrobial resistance coupled with consumer preferences towards natural preservatives has resulted in increased research towards investigating antimicrobial compounds from natural sources such as macroalgae (seaweeds), which contain antioxidant, antimicrobial, and anticancer compounds. This study investigates the antimicrobial activity of compounds [...] Read more.

A rise in antimicrobial resistance coupled with consumer preferences towards natural preservatives has resulted in increased research towards investigating antimicrobial compounds from natural sources such as macroalgae (seaweeds), which contain antioxidant, antimicrobial, and anticancer compounds. This study investigates the antimicrobial activity of compounds produced by the Irish seaweed Alaria esculenta against Escherichia coli and Listeria innocua, bacterial species which are relevant for food safety. Microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), ultrasound–microwave-assisted extraction (UMAE), and conventional extraction technologies (maceration) were applied to generate extracts from A. esculenta, followed by their preliminary chemical composition (total phenolic content, total protein content, total soluble sugars) and antimicrobial activity (with minimum inhibitory concentration determined by broth microdilution methods), examining also the molecular weight distribution (via high performance size exclusion chromatography) and oligosaccharide fraction composition (via high-performance liquid chromatography) of the polysaccharides, as they were the predominant compounds in these extracts, aiming to elucidate structure–function relationships. The chemical composition of the extracts demonstrated that they were high in total soluble sugars, with the highest total sugars being seen from the extract prepared with UAE, having 32.68 mg glucose equivalents/100 mg dried extract. Extracts had antimicrobial activity against E. coli and featured minimum inhibitory concentration (MIC) values of 6.25 mg/mL (in the case of the extract prepared with UAE) and 12.5 mg/mL (in the case of the extracts prepared with MAE, UMAE, and conventional maceration). No antimicrobial activity was seen by any extracts against L. innocua. An analysis of molar mass distribution of A. esculenta extracts showed high heterogeneity, with high-molecular-weight areas possibly indicating the presence of fucoidan. The FTIR spectra also indicated the presence of fucoidan as well as alginate, both of which are commonly found in brown seaweeds. These results indicate the potential of antimicrobials from seaweeds extracted using green technologies. Full article

(This article belongs to the Special Issue Marine Algae: Exploring Their Nutritional, Health, and Nutraceutical Potential)

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19 pages, 1653 KiB

Open AccessArticle

Bioactive Molecules from the Invasive Blue Crab Callinectes sapidus Exoskeleton: Evaluation of Reducing, Radical Scavenging, and Antitumor Activities

by Francesco Longo, Alessandro Attanzio, Laura Marretta, Claudio Luparello, Serena Indelicato, David Bongiorno, Giampaolo Barone, Luisa Tesoriere, Ilenia Concetta Giardina, Giulia Abruscato, Manuela Perlotti, Lucie Branwen Hornsby, Vincenzo Arizza, Mirella Vazzana, Aiti Vizzini, Chiara Martino, Angelica Listro, Vinicius Queiroz, Antonio Fabbrizio, Paolo Salvatore Francesco Ciaccio, Stella Maria Cascioferro, Francesca Di Gaudio and Manuela Mauro Show full author list Hide full author list

Mar. Drugs 2025, 23(1), 45; https://doi.org/10.3390/md23010045 - 17 Jan 2025

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Abstract

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source [...] Read more.

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source of chitosan, astaxanthin, and bio-phenolic compounds. These biomolecules were evaluated for their reducing, radical scavenging, and antitumor activity. The ferric ion reducing antioxidant power (FRAP) and the free radical scavenging activity against radical 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were significantly higher for chitosan (3.16 ± 0.10 mg AAE/g and 8.1 ± 0.10 µmol TE/g). No significant differences were observed among the tested biomolecules in their activity in scavenging the radical 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Both bio-phenolic compounds and astaxanthin exhibited dose-dependent cytotoxicity on CaCo-2 (IC₅₀ = 12.47 and 18 µg/mL) and HepG2 (IC₅₀ = 10.25 and 1.26 µg/mL) cell lines, while only bio-phenols showed no cytotoxic effect on differentiated CaCo-2 cells up to 20 µg/mL. These findings highlight the value of blue crab by-products in supporting a circular economy, offering a sustainable approach to managing this invasive species while providing bioactive compounds with promising medical and nutraceutical applications. Full article

(This article belongs to the Special Issue Marine Drug Research in Italy)

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16 pages, 2021 KiB

Open AccessArticle

Anthoteibinenes F–Q: New Sesquiterpenes from the Irish Deep-Sea Coral Anthothela grandiflora

by Stine S. H. Olsen, Sam Afoullouss, Ezequiel Cruz Rosa, Ryan M. Young, Mark Johnson, A. Louise Allcock and Bill. J. Baker

Mar. Drugs 2025, 23(1), 44; https://doi.org/10.3390/md23010044 - 17 Jan 2025

Viewed by 547

Abstract

New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral Anthothela grandiflora, [...] Read more.

New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral Anthothela grandiflora, we report 12 unreported cadinene-like functionalized sesquiterpenes, anthoteibinenes F–Q. The metabolites were isolated using both bioassay- and ¹H NMR-guided approaches. One-/two-dimensional NMR spectroscopy and high-resolution mass spectrometry were used for structure elucidation, while a combination of NOESY NMR experiments, GIAO NMR calculations coupled with DP4+ probabilities measures, and ECD comparisons were incorporated to propose relative and absolute configurations of the anthoteibinenes. The metabolites were screened against the Respiratory Syncytial Virus (RSV), ESKAPE pathogens, five Candida albicans strains, and one strain of C. auris. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)

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17 pages, 1859 KiB

Open AccessSystematic Review

Exploring Antibacterial Properties of Marine Sponge-Derived Natural Compounds: A Systematic Review

by Cintia Cristina Santi Martignago, Camila de Souza Barbosa, Homero Garcia Motta, Beatriz Soares-Silva, Erica Paloma Maso Lopes Peres, Lais Caroline Souza e Silva, Mirian Bonifácio, Karolyne dos Santos Jorge Sousa, Amanda Sardeli Alqualo, Júlia Parisi, Olivier Jordan, Ana Claudia Muniz Renno, Anna Caroline Campos Aguiar and Viorica Patrulea

Mar. Drugs 2025, 23(1), 43; https://doi.org/10.3390/md23010043 - 16 Jan 2025

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Abstract

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring [...] Read more.

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, as promising candidates for antimicrobial drugs. Marine sponges, in particular, are of interest because of their production of secondary metabolites (SM), which serve as chemical defenses against predators and pathogens. These metabolites exhibit a wide range of therapeutic properties, including antibacterial activity. This systematic review examines recent advancements in identifying new sponge-derived compounds with antimicrobial activity, specifically targeting Pseudomonas aeruginosa, a prevalent Gram-negative pathogen with the highest incidence rates in clinical settings. The selection criteria focused on antimicrobial compounds with reported Minimum Inhibitory Concentration (MIC) values. The identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, and bromotyrosine-derived derivatives. The structural features of the active compounds selected in this review may provide a foundational framework for developing new, highly bioactive antimicrobial agents. Full article

(This article belongs to the Special Issue Marine Natural Products with Antimicrobial Activity)

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24 pages, 4362 KiB

Open AccessFeature PaperArticle

Optimization of the Extraction Protocol for Pacific Ciguatoxins from Marine Products Prior to Analysis Using the Neuroblastoma Cell-Based Assay

by Thomas Yon, Philippe Cruchet, Jérôme Viallon, J. Sam Murray, Emillie Passfield, Mireille Chinain, Hélène Taiana Darius and Mélanie Roué

Mar. Drugs 2025, 23(1), 42; https://doi.org/10.3390/md23010042 - 16 Jan 2025

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Abstract

Ciguatera poisoning (CP) is caused by the consumption of marine products contaminated with ciguatoxins (CTXs) produced by dinoflagellates of the genus Gambierdiscus. Analytical methods for CTXs, involving the extraction/purification of trace quantities of CTXs from complex matrices, are numerous in the literature. [...] Read more.

Ciguatera poisoning (CP) is caused by the consumption of marine products contaminated with ciguatoxins (CTXs) produced by dinoflagellates of the genus Gambierdiscus. Analytical methods for CTXs, involving the extraction/purification of trace quantities of CTXs from complex matrices, are numerous in the literature. However, little information on their effectiveness for nonpolar CTXs is available, yet these congeners, contributing to the risk of CP, are required for the establishment of effective food safety monitoring programs. An evaluation of six extraction/purification protocols, performed with CTX3C spiked on fish flesh and a neuroblastoma cell-based assay (CBA-N2a), revealed recoveries from 6 to 45%. This led to the development of an optimized 3-day protocol designed for a large number of samples, with CTX1B and CTX3C eluting in a single fraction and showing recoveries of 73% and 70%, respectively. In addition, a reduction in adverse matrix effects in the CBA-N2a analyses was demonstrated with naturally contaminated specimens, increasing the sensitivity of the method, which now meets the very low guidance level recommended by international agencies. However, efforts are still required to reduce the signal suppression observed in LC-MS/MS analysis. This optimized protocol contributes to the technological advancement of detection methods, promoting food safety and improving CP risk assessment in marine products. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section "Marine Toxins")

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23 pages, 2860 KiB

Open AccessArticle

Novel Insights into the Nobilamide Family from a Deep-Sea Bacillus: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria

by Vincenza Casella, Gerardo Della Sala, Silvia Scarpato, Carmine Buonocore, Costanza Ragozzino, Pietro Tedesco, Daniela Coppola, Giovanni Andrea Vitale, Donatella de Pascale and Fortunato Palma Esposito

Mar. Drugs 2025, 23(1), 41; https://doi.org/10.3390/md23010041 - 14 Jan 2025

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Abstract

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection [...] Read more.

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase. Full article

(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)

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17 pages, 2531 KiB

Open AccessArticle

Optimization of a Sonotrode Extraction Method and New Insight of Phenolic Composition of Fucus vesiculosus

by Lidia Gil-Martínez, Alejandro Santos-Mejías, José Manuel De la Torre-Ramírez, Alberto Baños, Vito Verardo and Ana M. Gómez-Caravaca

Mar. Drugs 2025, 23(1), 40; https://doi.org/10.3390/md23010040 - 14 Jan 2025

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Abstract

The optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were [...] Read more.

The optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were selected to maximize phenolic recovery while considering environmental and energy sustainability by optimizing extraction efficiency and minimizing solvent and energy usage. HPLC-ESI-QTOF-MS analysis tentatively identified 25 phenolic compounds, including sulfated phenolic acids, phlorotannins, flavonoids, and halophenols, with some reported for the first time in F. vesiculosus, underscoring the complexity of this alga’s metabolome. The antioxidant activity of the optimized extract was evaluated through FRAP (143.7 µmol TE/g), DPPH (EC₅₀ 105.6 µg/mL), and TEAC (189.1 µmol Trolox/g) assays. The optimized process highlights F. vesiculosus as a valuable source of natural antioxidants, with potential applications in biotechnology, cosmetics, and food industries. Full article

(This article belongs to the Special Issue Therapeutic Potential of Phlorotannins)

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26 pages, 4179 KiB

Open AccessReview

Actinomycete-Derived Pigments: A Path Toward Sustainable Industrial Colorants

by Blanca Hey Díez, Cristiana A. V. Torres and Susana P. Gaudêncio

Mar. Drugs 2025, 23(1), 39; https://doi.org/10.3390/md23010039 - 13 Jan 2025

Viewed by 1011

Abstract

Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, [...] Read more.

Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, pigments remain essential across numerous industries, including the cosmetic, textile, food, automotive, paints and coatings, plastics, and packaging industries. In response to growing consumer demand for sustainable options, there is increasing interest in eco-friendly alternatives, particularly bio-based pigments derived from algae, fungi, and actinomycetes. This shift is largely driven by consumer demand for sustainable options. For bio-pigments, actinomycetes, particularly from the Streptomyces genus, have emerged as a promising green source, aligning with global sustainability goals due to their renewability and biodegradability. Scale-up of production and yield optimization challenges have been circumvented with the aid of biotechnology advancements, including genetic engineering and innovative fermentation and extraction methods, which have enhanced these bio-pigments’ viability and cost-competitiveness. Actinomycete-derived pigments have successfully transitioned from laboratory research to commercialization, showcasing their potential as sustainable and eco-friendly alternatives to synthetic dyes. With the global pigment market valued at approximately USD 24.28 billion in 2023, which is projected to reach USD 36.58 billion by 2030, the economic potential for actinomycete pigments is extensive. This review explores the environmental advantages of actinomycete pigments, their role in modern industry, and the regulatory and commercialization challenges they face, highlighting the importance of these pigments as promising solutions to reduce our reliance on conventional toxic pigments. The successful commercialization of actinomycete pigments can drive an industry-wide transition to environmentally responsible alternatives, offering substantial benefits for human health, safety, and environmental sustainability. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section “Marine Biotechnology Related to Drug Discovery or Production”)

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14 pages, 2676 KiB

Open AccessArticle

Polysaccharide Fraction Isolated from Saccharina japonica Exhibits Anti-Cancer Effects Through Immunostimulating Activities

by Min Seung Park, Seung-U Son, Tae Eun Kim, Se Hyun Shim, Bong-Keun Jang, Sunyoung Park and Kwang-Soon Shin

Mar. Drugs 2025, 23(1), 38; https://doi.org/10.3390/md23010038 - 13 Jan 2025

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Abstract

The present research aimed to assess the anti-cancer effects of the polysaccharide fraction (SJP) isolated from Saccharina japonica. The release of immune-activating cytokines, including IL-6, IL-12, and TNF-α, was markedly stimulated by the SJP in a concentration-dependent manner within the range of [...] Read more.

The present research aimed to assess the anti-cancer effects of the polysaccharide fraction (SJP) isolated from Saccharina japonica. The release of immune-activating cytokines, including IL-6, IL-12, and TNF-α, was markedly stimulated by the SJP in a concentration-dependent manner within the range of 1 to 100 µg/mL. Furthermore, the prophylactic intravenous (p.i.v.) and per os (p.p.o.) injection of SJP boosted the cytolytic activity mediated by NK cells and CTLs against tumor cells. In a study involving Colon26-M3.1 carcinoma as a lung cancer model, both p.i.v. and p.p.o. exhibited significant anti-lung-cancer effects. Notably, p.i.v. and p.p.o. administration of SJP at a dose of 50 mg/kg reduced tumor colonies by 84% and 40%, respectively, compared to the control. Moreover, the anti-lung-cancer effects of SJP remained substantial, even when NK cell function was inhibited using anti-asialo-GM1. Fractionation with CaCl₂ suggested that SJP is a mixture of alginate and fucoidan. The fucoidan fraction stimulated the immune response of macrophages more strongly than the alginate fraction. Consequently, this finding suggested that SJP from S. japonica possesses remarkable anti-cancer effects through the activation of various immunocytes. In addition, this finding indicates that the potent biological activity of SJP may be attributed to fucoidan. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)

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21 pages, 717 KiB

Open AccessReview

Fatty Acids in Cnidaria: Distribution and Specific Functions

by Vasily I. Svetashev

Mar. Drugs 2025, 23(1), 37; https://doi.org/10.3390/md23010037 - 13 Jan 2025

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Abstract

The phylum Cnidaria comprises five main classes—Hydrozoa, Scyphozoa, Hexacorallia, Octocorallia and Cubozoa—that include such widely distributed and well-known animals as hard and soft corals, sea anemones, sea pens, gorgonians, hydroids, and jellyfish. Cnidarians play a very important role in marine ecosystems. The composition [...] Read more.

The phylum Cnidaria comprises five main classes—Hydrozoa, Scyphozoa, Hexacorallia, Octocorallia and Cubozoa—that include such widely distributed and well-known animals as hard and soft corals, sea anemones, sea pens, gorgonians, hydroids, and jellyfish. Cnidarians play a very important role in marine ecosystems. The composition of their fatty acids (FAs) depends on food (plankton and particulate organic matter), symbiotic photosynthetic dinoflagellates and bacteria, and de novo biosynthesis in host tissues. In cnidarian lipids, besides the common FA characteristics of marine organisms, numerous new and rare FAs are also found. All Octocorallia species and some Scyphozoa jellyfish contain polyunsaturated FAs (PUFAs) with 24 and 26 carbon atoms. The coral families can be distinguished by specific FA profiles: the presence of uncommon FAs or high/low levels of common fatty acids. Many of the families have characteristic FAs: Acroporidae are characterized by 18:3n6, eicosapentaenoic acid (EPA) 20:5n3, 22:4n6, and 22:5n3; Pocilloporidae by 20:3n6, 20:4n3, and docosahexaenoic acid 22:6n3 (DHA); and Poritidae by arachidonic acid (AA) and DHA. The species of Faviidae show elevated concentrations of 18:3n6 and 22:5n3 acids. Dendrophylliidae, being azooxanthellate corals, have such dominant acids as EPA and 22:5n3 and a low content of DHA, which is the major PUFA in hermatypic corals. The major and characteristic PUFAs for Milleporidae (class Hydrozoa) are DHA and 22:5n6, though in scleractinian corals, the latter acid is found only in trace amounts. Full article

(This article belongs to the Special Issue Fatty Acids from Marine Organisms, 2nd Edition)

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12 pages, 1562 KiB

Open AccessArticle

Bioactive Steroids with Structural Diversity from the South China Sea Soft Coral Lobophytum sp. and Sponge Xestospongia sp.

by Lin-Mao Ke, Zi-Ru Zhang, Song-Wei Li, Yan-Bo Zeng, Ming-Zhi Su and Yue-Wei Guo

Mar. Drugs 2025, 23(1), 36; https://doi.org/10.3390/md23010036 - 13 Jan 2025

Viewed by 557

Abstract

A chemical investigation of the soft coral Lobophytum sp. and the sponge Xestospongia sp. from the South China Sea led to the isolation of five steroids, including two new compounds (1 and 4) and one known natural product (3). [...] Read more.

A chemical investigation of the soft coral Lobophytum sp. and the sponge Xestospongia sp. from the South China Sea led to the isolation of five steroids, including two new compounds (1 and 4) and one known natural product (3). Compounds 1–3 were derived from the soft coral Lobophytum sp., while 4 and 5 were obtained from the sponge Xestospongia sp. The structures of these compounds were determined by extensive spectroscopic analysis, the time-dependent density functional theory–electronic circular dichroism (TDDFT-ECD) calculation method, and comparison with the spectral data previously reported in the literature. The antibacterial and anti-inflammatory activities of isolated compounds were evaluated in vitro. Compounds 1–3, 4, and 5 exhibited weak antibacterial activity against vancomycin-resistant Enterococcus faecium G1, Streptococcus parauberis KSP28, Photobacterium damselae FP2244, Lactococcus garvieae FP5245, and Pseudomonas aeruginosa ZJ028. Moreover, compound 3 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with an IC₅₀ value of 13.48 μM. Full article

(This article belongs to the Special Issue Bioactive Compounds from Soft Corals and Their Derived Microorganisms)

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20 pages, 679 KiB

Open AccessArticle

Antioxidant and Anti-Obesity Properties of Acidic and Alkaline Seaweed Extracts Adjusted to Different pH Levels

by Sakhi Ghelichi, Mona Hajfathalian, Sara Falcione and Charlotte Jacobsen

Mar. Drugs 2025, 23(1), 35; https://doi.org/10.3390/md23010035 - 12 Jan 2025

Viewed by 984

Abstract

This research examined antioxidant and anti-obesity effects of Palmaria palmata extracts obtained through acidic or alkaline treatments and subsequent pH adjustments. After two rounds of acidic or alkaline extraction, the extracts were separated from biomass and adjusted to different pH values: for acidic [...] Read more.

This research examined antioxidant and anti-obesity effects of Palmaria palmata extracts obtained through acidic or alkaline treatments and subsequent pH adjustments. After two rounds of acidic or alkaline extraction, the extracts were separated from biomass and adjusted to different pH values: for acidic extracts, pH 3 (no adjustment), pH 6, pH 9, and pH 12; for alkaline extracts, pH 12 (no adjustment), pH 9, pH 6, and pH 3. The findings revealed that extraction medium as well as subsequent pH adjustments significantly influenced composition of the extracts in terms of protein content and recovery, amino acids, and phenolic compounds (p < 0.05). Acidic conditions produced extracts with potent radical scavenging, especially at pH 6 (IC₅₀ = 0.30 ± 0.04 mg.mL⁻¹), while alkaline conditions favored metal chelating, with the highest Fe²⁺ chelation at pH 12 (IC₅₀ = 0.65 ± 0.03 mg.mL⁻¹). Moreover, extracts showed inhibitory activities against porcine pancreatic lipase and α-amylase, with the acidic extract at pH 9 showing the best anti-obesity properties (IC₅₀ = 5.38 ± 0.34 mg.mL⁻¹ for lipase and IC₅₀ = 5.79 ± 0.30 mg.mL⁻¹ for α-amylase). However, the highest α-amylase activity was in the alkaline extract at pH 12 (IC₅₀ = 3.05 ± 0.66 mg.mL⁻¹). In conclusion, adjusting the pH of seaweed extracts notably influences their bioactive properties, likely due to changes in the reactivity and interactions of bioactive compounds such as peptides, carbohydrates, and polyphenols. Full article

(This article belongs to the Special Issue The Bioactive Potential of Marine-Derived Peptides and Proteins)

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46 pages, 15366 KiB

Open AccessFeature PaperReview

Investigating Past, Present, and Future Trends on Interface Between Marine and Medical Research and Development: A Bibliometric Review

by Mehdi Zamani, Tetyana Melnychuk, Anton Eisenhauer, Ralph Gäbler and Carsten Schultz

Mar. Drugs 2025, 23(1), 34; https://doi.org/10.3390/md23010034 - 10 Jan 2025

Viewed by 827

Abstract

The convergence of marine sciences and medical studies has the potential for substantial advances in healthcare. This study uses bibliometric and topic modeling studies to map the progression of research themes from 2000 to 2023, with an emphasis on the interdisciplinary subject of [...] Read more.

The convergence of marine sciences and medical studies has the potential for substantial advances in healthcare. This study uses bibliometric and topic modeling studies to map the progression of research themes from 2000 to 2023, with an emphasis on the interdisciplinary subject of marine and medical sciences. Building on the global publication output at the interface between marine and medical sciences and using the Hierarchical Dirichlet Process, we discovered dominating research topics during three periods, emphasizing shifts in research focus and development trends. Our data show a significant rise in publication output, indicating a growing interest in using marine bioresources for medical applications. The paper identifies two main areas of active research, “natural product biochemistry” and “trace substance and genetics”, both with great therapeutic potential. We used social network analysis to map the collaborative networks and identify the prominent scholars and institutions driving this research and development progress. Our study indicates important paths for research policy and R&D management operating at the crossroads of healthcare innovation and marine sciences. It also underscores the significance of quantitative foresight methods and interdisciplinary teams in identifying and interpreting future scientific convergences and breakthroughs. Full article

(This article belongs to the Special Issue From Seaside to Bedside: Dedicated to Professor José María Fernández Sousa-Faro)

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30 pages, 6831 KiB

Open AccessReview

Recent Advances in Natural Products Derived from Marine Echinoderms and Endophytic Microbes: Chemical Insights and Therapeutic Potential

by Shuangyu Li, Yan Xiao, Qiang Li, Mingzhi Su, Yuewei Guo and Xin Jin

Mar. Drugs 2025, 23(1), 33; https://doi.org/10.3390/md23010033 - 10 Jan 2025

Viewed by 893

Abstract

Echinoderms, a diverse group of marine invertebrates including starfish, sea urchins, and sea cucumbers, have been recognized as prolific sources of structurally diverse natural products. In the past five years, remarkable progress has been made in the isolation, structural elucidation, and pharmacological assessment [...] Read more.

Echinoderms, a diverse group of marine invertebrates including starfish, sea urchins, and sea cucumbers, have been recognized as prolific sources of structurally diverse natural products. In the past five years, remarkable progress has been made in the isolation, structural elucidation, and pharmacological assessment of these bioactive compounds. These metabolites, including polysaccharides, triterpenoids, steroids, and peptides, demonstrate potent bioactivities such as anticancer, anti-inflammatory, antiviral, and antimicrobial effects, providing valuable insights and scaffolds for drug discovery. This review highlights the structural diversity and biological activities of natural products derived from echinoderms over the last five years, with a particular focus on their structure–activity relationships and therapeutic potential. It also outlines the prospects and challenges for future research, aiming to stimulate further exploration in marine drug discovery. Full article

(This article belongs to the Special Issue From Seaside to Bedside: Dedicated to Professor José María Fernández Sousa-Faro)

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21 pages, 4921 KiB

Open AccessArticle

Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma

by Angélica Luna-Nophal, Fernando Díaz-Castillo, Vanessa Izquierdo-Sánchez, Jesús B. Velázquez-Fernández, Mario Orozco-Morales, Luis Lara-Mejía, Johana Bernáldez-Sarabia, Noemí Sánchez-Campos, Oscar Arrieta, José Díaz-Chávez, Jorge-Ismael Castañeda-Sánchez, Alexei-Fedorovish Licea-Navarro and Saé Muñiz-Hernández

Mar. Drugs 2025, 23(1), 32; https://doi.org/10.3390/md23010032 - 10 Jan 2025

Viewed by 668

Abstract

Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some [...] Read more.

Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules. This study analyzed the anticancer effects in vitro and in vivo of two peptides found in C. californicus. The effects of s-cal14.1b and s-cal14.2b on cell proliferation, apoptosis, and cytotoxicity were evaluated in 2D and 3D cultures of MPM-derived cells. Proteomics analysis of 3D cultures treated with conotoxins was performed to examine changes in expression or abundance. And the therapeutic effects of both conotoxins were evaluated in MPM mouse xenografts. s-cal14.1b and s-cal14.2b induced apoptosis and cytotoxicity in 2D and 3D cultures. However, only s-cal14.1b modified spheroid growth. Approximately 600 proteins exhibited important differential expression, which was more heterogeneous in H2452 vs MSTO-211H spheroids. The in silico protein functional analysis showed modifications in the biological pathways associated with carcinogenesis. CAPN1, LIMA1, ANXA6, HUWE1, PARP1 or PARP4 proteins could be potential cell targets for conotoxins and serve as biomarkers in MPM. Finally, we found that both conotoxins reduced the tumor mass in MPM xenografts; s-cal14.1b reached statistical significance. Based on these results, s-cal14.1b and s-cal14.2b conotoxins could be potential therapeutic drugs for MPM neoplasms with no apparent side effects on normal cells. Full article

(This article belongs to the Special Issue Conotoxins: Detection, Classification and Potential Therapeutic Benefits)

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14 pages, 2574 KiB

Open AccessArticle

Protective Effects of Chitosan Oligosaccharide Against Lipopolysaccharide-Induced Inflammatory Response and Oxidative Stress in Bovine Mammary Epithelial Cells

by Ziwei Lin, Yanlong Zhou, Ruiwen Chen, Qiuyan Tao, Qiwen Lu, Qianchao Xu, Haibin Yu, Ping Jiang and Zhihui Zhao

Mar. Drugs 2025, 23(1), 31; https://doi.org/10.3390/md23010031 - 9 Jan 2025

Viewed by 465

Abstract

Chitosan oligosaccharide (COS) is receiving increasing attention as a feed additive in animal production. COS has a variety of biological functions, including anti-inflammatory and antioxidant activities. Mastitis is a major disease in dairy cows that has a significant impact on animal welfare and [...] Read more.

Chitosan oligosaccharide (COS) is receiving increasing attention as a feed additive in animal production. COS has a variety of biological functions, including anti-inflammatory and antioxidant activities. Mastitis is a major disease in dairy cows that has a significant impact on animal welfare and production. Hence, this research aimed to investigate the mechanism of COS on the lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in bovine mammary epithelial cells (BMECs). In this study, the results demonstrated that COS protected BMECs from the inflammatory response induced by LPS by restraining the excessive production of toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). COS treatment also suppressed excessive reactive oxygen species (ROS) production and restored antioxidant enzyme activity under LPS-induced oxidative stress conditions. Furthermore, the results also demonstrated that COS promote nuclear factor erythroid 2-related factor 2 (Nrf2) expression and inhibit TLR4 levels and p65 and IκBα phosphorylation in BMECs exposed to LPS. In summary, the results demonstrate that the protective mechanism of COS on the LPS-induced inflammatory response and oxidative stress depend on the TLR4/nuclear factor-κB (NF-κB) and Nrf2 signaling pathways, indicating that COS could serve as natural protective agents for alleviating BMECs in mastitis. Full article

(This article belongs to the Special Issue Marine Natural Products and Signaling Pathways, 2nd Edition)

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26 pages, 4334 KiB

Open AccessArticle

Biochemical Composition and Seasonal Variations of the Madagascar Algae Eucheuma denticulatum (Solieriaceae, Rhodophyta)

by Elando Fréda Zamanileha, Anne-Sophie Burlot, Thomas Latire, Christel Marty, Philippe Douzenel, Laurent Vandanjon, Nathalie Bourgougnon, Pierre Ravelonandro and Gilles Bedoux

Mar. Drugs 2025, 23(1), 30; https://doi.org/10.3390/md23010030 - 9 Jan 2025

Viewed by 637

Abstract

Although the density and diversity of seaweeds in Madagascar is particularly high, these resources are underexploited and they are not part of the local population’s eating habits. No study has been carried out on the nutritional properties and seasonal variation of Eucheuma species [...] Read more.

Although the density and diversity of seaweeds in Madagascar is particularly high, these resources are underexploited and they are not part of the local population’s eating habits. No study has been carried out on the nutritional properties and seasonal variation of Eucheuma species harvested in Madagascar. In this study, Eucheuma denticulatum was harvested monthly over two years (2021 and 2022) on the northeast coast of Madagascar (Sainte Marie Island). The compositional analysis revealed prominent sugars and minerals up to 41.0 and 39.5% dw, respectively. E. denticulatum showed slight variability over the seasons in the macroelements and oligoelements (Ca, K, Na, Mg, Fe, Mn) ranging from 22.8 ± 0.2 to 25.3 ± 0.1% dw in 2021 and 22.1 ± 0.3 to 26.5 ± 0.3% dw in 2022. Total amino acids varied from 2.3 ± 0.6 to 2.5 ± 0.6% dw during the two years. Seaweed extracts showed antioxidant activity by the in vitro method ranging from 2026 ± 2 to 2998 ± 4 μg.mL⁻¹ in 2021, and from 1904 ± 2 to 2876 ± 4 μg.mL⁻¹ in 2022. Finally, the principal component analysis (PCA) showed a correlation between protein content and environmental parameters. The nutritional characteristics therefore confirmed that E. denticulatum could potentially be used as a nutritious and functional food and could be incorporated in the diet of local populations. Full article

(This article belongs to the Special Issue Bioactive Polysaccharides from Seaweeds)

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16 pages, 8075 KiB

Open AccessArticle

Structure of a Sulfated Capsular Polysaccharide from the Marine Bacterium Cobetia marina KMM 1449 and a Genomic Insight into Its Biosynthesis

by Maxim S. Kokoulin, Yulia V. Savicheva, Alina P. Filshtein, Ludmila A. Romanenko and Marina P. Isaeva

Mar. Drugs 2025, 23(1), 29; https://doi.org/10.3390/md23010029 - 8 Jan 2025

Viewed by 636

Abstract

Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, [...] Read more.

Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, the capsular polysaccharide (CPS) was obtained from the bacterium Cobetia marina KMM 1449, isolated from a marine sediment sample collected along the shore of the Sea of Japan. The CPS was isolated by saline solution, purified by a series of chromatographic procedures, and studied by chemical methods along with 1D and 2D ¹H and ¹³C NMR spectroscopy. The following new structure of the CPS from C. marina KMM 1449 was established and consisted of sulfated and simultaneously phosphorylated disaccharide repeating units: →4)-α-L-Rhap2S-(1→3)-β-D-Manp6PGro-(1→. To elucidate the genetic basis of the CPS biosynthesis, the whole genomic sequence of C. marina KMM 1449 was obtained. The CPS biosynthetic gene cluster (BGC) of about 70 genes composes four regions encoding nucleotide sugar biosynthesis (dTDP-Rha and GDP-Man), assembly (GTs genes), translocation (ABC transporter genes), sulfation (PAPS biosynthesis and sulfotransferase genes) and lipid carrier biosynthesis (wcb operon). Comparative analysis of the CPS BGCs from available Cobetia genomes showed the presence of KMM 1449-like CPS BGC among strains of all three Cobetia species. The study of new natural sulfated polysaccharides, as well as the elucidation of the pathways of their biosynthesis, provides the basis for the development of potential anticancer drugs. Full article

(This article belongs to the Special Issue Exopolysaccharide Isolated from Marine Microorganisms)

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14 pages, 1768 KiB

Open AccessArticle

Expression Analysis of Heavy-Chain-Only Antibodies in Cloudy Catshark and Japanese Bullhead Shark

by Reo Uemura, Susumu Tanimura, Nao Yamaguchi, Ryuichi Kuroiwa, Gabriel Takashi Andrés Tsutsumi, Toshiaki Fujikawa, Kiyoshi Soyano, Kohsuke Takeda and Yoshimasa Tanaka

Mar. Drugs 2025, 23(1), 28; https://doi.org/10.3390/md23010028 - 8 Jan 2025

Viewed by 654

Abstract

Heavy chain-only antibodies in sharks are called immunoglobulin new antigen receptors (IgNAR), consisting of one variable region (VNAR) and five constant regions (C1-C5). The variable region of IgNAR can be expressed as a monomer composed of a single domain, which has antigen specificity [...] Read more.

Heavy chain-only antibodies in sharks are called immunoglobulin new antigen receptors (IgNAR), consisting of one variable region (VNAR) and five constant regions (C1-C5). The variable region of IgNAR can be expressed as a monomer composed of a single domain, which has antigen specificity and is thus gaining attention as a next-generation antibody drug modality. In this study, we analyzed IgNAR of the cloudy catshark and Japanese bullhead shark, small demersal sharks available in the coastal waters of Japan. By analyzing the IgNAR gene sequence and comparing it with the constant regions of five other known shark species, high homology was observed in the C4 region. Consequently, we expressed the recombinant protein of the C4 domain from the cloudy catshark in E. coli, immunized rats, and produced antibodies. The obtained antiserum and mAbs recognized the C4 recombinant protein of the cloudy catshark, but reacted minimally with the plasma of non-immunized cloudy catsharks and instead reacted with the plasma of Japanese bullhead sharks. The results of this study imply that the protein expression levels of IgNAR in cloudy catsharks may be relatively lower compared to those in Japanese bullhead sharks, however, this interpretation remains to be determined through further studies. Full article

(This article belongs to the Special Issue A Deep Dive into the Ocean: Evaluation of Marine Compounds Bioactivity in the Omics Era)

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36 pages, 4076 KiB

Open AccessReview

A Comparative Review of Alternative Fucoidan Extraction Techniques from Seaweed

by Matthew Chadwick, Loïc G. Carvalho, Carlos Vanegas and Simone Dimartino

Mar. Drugs 2025, 23(1), 27; https://doi.org/10.3390/md23010027 - 7 Jan 2025

Viewed by 1594

Abstract

Fucoidan is a sulfated polysaccharide found in brown seaweed. Due to its reported biological activities, including antiviral, antibacterial and anti-inflammatory activities, it has garnered significant attention for potential biomedical applications. However, the direct relationship between fucoidan extracts’ chemical structures and bioactivities is unclear, [...] Read more.

Fucoidan is a sulfated polysaccharide found in brown seaweed. Due to its reported biological activities, including antiviral, antibacterial and anti-inflammatory activities, it has garnered significant attention for potential biomedical applications. However, the direct relationship between fucoidan extracts’ chemical structures and bioactivities is unclear, making it extremely challenging to predict whether an extract will possess a given bioactivity. This relationship is further complicated by a lack of uniformity in the recent literature in terms of the assessment and reporting of extract properties, yield and chemical composition (e.g., sulfate, fucose, uronic acid and monosaccharide contents). These inconsistencies pose significant challenges when directly comparing extraction techniques across studies. This review collected data on extract contents and properties from a selection of available studies. Where information was unavailable directly, efforts were made to extrapolate data. This approach enabled a comprehensive examination of the correlation between extraction techniques and the characteristics of the resulting extracts. A holistic framework is presented for the selection of fucoidan extraction methods, outlining key heuristics to consider when capturing the broader context of a seaweed bioprocess. Future work should focus on developing knowledge within these heuristic categories, such as the creation of technoeconomic models of each extraction process. This framework should allow for a robust extraction selection process that integrates process scale, cost and constraints into decision making. Key quality attributes for biologically active fucoidan are proposed, and areas for future research are identified, such as studies for specific bioactivities aimed at elucidating fucoidan’s mechanism of action. This review also sets out future work required to standardize the reporting of fucoidan extract data. Standardization could positively enhance the quality and depth of data on fucoidan extracts, enabling the relationships between physical, chemical and bioactive properties to be identified. Recommendations on best practices for the production of high-quality fucoidan with desirable yield, characteristics and bioactivity are highlighted. Full article

(This article belongs to the Special Issue Marine Polysaccharides and Oligosaccharides: Extraction and Biological Activities)

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16 pages, 2308 KiB

Open AccessArticle

A Comparative Study of the In Vitro Intestinal Permeability of Pinnatoxins and Portimine

by Rachelle Lanceleur, Vincent Hort, Marion Peyrat, Denis Habauzit, Andrew I. Selwood and Valérie Fessard

Mar. Drugs 2025, 23(1), 26; https://doi.org/10.3390/md23010026 - 7 Jan 2025

Viewed by 544

Abstract

The pinnatoxins (PnTXs) and portimines, produced by Vulcanodinium rugosum, have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body [...] Read more.

The pinnatoxins (PnTXs) and portimines, produced by Vulcanodinium rugosum, have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body after oral administration. Therefore, we investigated the impact of PnTX analogs (PnTX-A, -E, -F, -G, and -H) and portimine (8, 16, and 32 ng/mL) on intestinal barrier integrity and their oral bioavailability using human Caco-2 cell monolayers treated for 2, 6, and 24 h. Our results demonstrated that all of the toxins could impair barrier integrity after 24 h, with differences observed for PnTX-A, -E, and -F, as well as portimine, the most potent of all. While PnTX-A and -E exhibited poor permeability, the other PnTXs were more penetrative, with a Papp > 1.5 × 10⁻⁶ cm·s⁻¹. Portimine was the only toxin displaying both a time- and concentration-dependent passage, likely involving a passive diffusion process. The experimental results were compared to predictions obtained by QSAR tools. Although only qualitative, our results suggest that some of these compounds may be more likely to be distributed throughout the body. Further in vivo studies are required to estimate oral bioavailability and potential public health concerns. Full article

(This article belongs to the Special Issue Marine Biotoxins 3.0)

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48 pages, 3635 KiB

Open AccessReview

Bioactive Angucyclines/Angucyclinones Discovered from 1965 to 2023

by Hai-Shan Liu, Hui-Ru Chen, Shan-Shan Huang, Zi-Hao Li, Chun-Ying Wang and Hua Zhang

Mar. Drugs 2025, 23(1), 25; https://doi.org/10.3390/md23010025 - 5 Jan 2025

Viewed by 678

Abstract

Angucyclines/angucyclinones, a class of polyketides with diverse chemical structures, display various bioactivities including antibacterial or antifungal, anticancer, anti-neuroinflammatory, and anti-α-glucosidase activities. Marine and terrestrial microorganisms have made significant contributions to the discovery of bioactive angucyclines/angucyclinones. This review covers 283 bioactive angucyclines/angucyclinones discovered from [...] Read more.

Angucyclines/angucyclinones, a class of polyketides with diverse chemical structures, display various bioactivities including antibacterial or antifungal, anticancer, anti-neuroinflammatory, and anti-α-glucosidase activities. Marine and terrestrial microorganisms have made significant contributions to the discovery of bioactive angucyclines/angucyclinones. This review covers 283 bioactive angucyclines/angucyclinones discovered from 1965 to 2023, and the emphasis is on the biological origins, chemical structures, and biological activities of these interesting natural products. Full article

(This article belongs to the Special Issue Natural Products Isolated from Marine Sediment)

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21 pages, 8475 KiB

Open AccessArticle

Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design

by Ningying Zheng, Xuan Li, Nan Zhou and Lianxiang Luo

Mar. Drugs 2025, 23(1), 24; https://doi.org/10.3390/md23010024 - 5 Jan 2025

Viewed by 705

Abstract

LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore [...] Read more.

LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore models. Six compounds were optimized for protein binding after being docked against the positive control Compound A. Two compounds showed promising results in ADMET screening. Molecular dynamics simulations were utilized to predict binding mechanisms, with Compound 69081_50 identified as a potential LCN2 inhibitor. MM-PBSA analysis revealed key amino acid residues that are involved in interactions, suggesting that Compound 69081_50 could be a candidate for drug development. Full article

(This article belongs to the Special Issue Chemoinformatics for Marine Drug Discovery)

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15 pages, 6024 KiB

Open AccessArticle

Identification of Filovirus Entry Inhibitors from Marine Fungus-Derived Indole Alkaloids

by Leah Liu Wang, Javier Seravalli, Brett Eaton, Yi Liu, Michael R. Holbrook, Wen-Jian Lan and Shi-Hua Xiang

Mar. Drugs 2025, 23(1), 23; https://doi.org/10.3390/md23010023 - 3 Jan 2025

Viewed by 881

Abstract

Filoviruses, mainly consisting of the two genera of Ebolavirus and Marburgvirus, are enveloped negative-strand RNA viruses that can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. However, we still do not have effective medicines for treating these [...] Read more.

Filoviruses, mainly consisting of the two genera of Ebolavirus and Marburgvirus, are enveloped negative-strand RNA viruses that can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. However, we still do not have effective medicines for treating these diseases. To search for effective drugs, we have identified three marine indole alkaloids that exhibit potent activities against filovirus infection. Thus, it is suggested that marine indole alkaloids can be a valuable compound source for filovirus drug screening and development. Since marine indole alkaloids comprise a large diverse group of secondary metabolites, their biological properties would be helpful for pharmaceutical drug development to treat various filovirus infections. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

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13 pages, 7126 KiB

Open AccessArticle

Selenium–Chondroitin Sulfate Nanoparticles Inhibit Angiogenesis by Regulating the VEGFR2-Mediated PI3K/Akt Pathway

by Xia Zheng, Xiaofei Liu, Zhuo Wang, Rui Li, Qiaoli Zhao, Bingbing Song, Kit-Leong Cheong, Jianping Chen and Saiyi Zhong

Mar. Drugs 2025, 23(1), 22; https://doi.org/10.3390/md23010022 - 2 Jan 2025

Viewed by 780

Abstract

Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate [...] Read more.

Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na₂SeO₃) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor. Full article

(This article belongs to the Special Issue Marine Polysaccharides and Oligosaccharides: Extraction and Biological Activities)

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13 pages, 1677 KiB

Open AccessArticle

Pilot-Scale Enzymatic Conversion of Low Stability, High Free Fatty, Squid Oil to an Oxidatively Stable Astaxanthin-Rich Acylglyceride Oil Suitable for Nutritional Applications

by Asavari Joshi, Brendan Holland, Moninder Sachar and Colin J. Barrow

Mar. Drugs 2025, 23(1), 21; https://doi.org/10.3390/md23010021 - 2 Jan 2025

Viewed by 580

Abstract

Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid [...] Read more.

Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid oil using immobilized lipase (Lipozyme RMIM) was demonstrated, resulting in high acylglyceride yields. The processed oil was analyzed for oxidation kinetics and thermodynamics using Rancimat, fatty acid composition using GC, omega-3 fatty acid positional distribution in the acylglyceride product using ¹³C NMR, and astaxanthin content. Lipase treatment reduced FFA levels from 44% to 4% and increased acylglycerides to 93% in squid oil. This reduction in FFA was accompanied by significantly increased stability (0.06 to 18.9 h by Rancimat). The treated oil showed no loss in astaxanthin (194.1 µg/g) or omega-3 fatty acids, including docosahexaenoic acid (DHA). DHA remaining predominantly at sn-2 indicated that the naturally occurring positional distribution of this omega-3 FFA was retained in the product. Lipase treatment significantly enhanced oxidative stability, evidenced by improved thermodynamic parameters (E_a 94.15 kJ/mol, ΔH 91.09 kJ/mol, ΔS −12.6 J/mol K) and extended shelf life (IP₂₅ 74.42 days) compared to starting squid oil and commercial fish/squid oils lacking astaxanthin. Thus, lipase treatment offers an effective strategy for reducing FFA levels and producing oxidatively stable, astaxanthin-rich acylglyceride squid oil with DHA retained at the nutritionally favored sn-2 position. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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